Bones, heart and the new anabolic agent romosozumab

Abstract

Osteoporosis is the result of a long process where resorption exceeds formation, compromising the cancellous and cortical microstructure of the bone and thus affecting its strength and increasing significantly the risk of fracture. To stop this process, we used, and are still using, antiresorptives, mainly bisphosphonates.1 Interestingly, this year we celebrate their 50th anniversary. The potential to reconstruct the skeleton materialised in 2002 with the introduction of teriparatide, a recombinant human parathyroid hormone (PTH) consisting of its N-terminal only fragment (aa 1–34). It is administered subcutaneously one time per day. The approved dose is 20 mcg and the use of the drug for more than 2 years during a patient’s lifetime is not recommended. In 2017, abaloparatide, a PTH-related protein analogue, became the second US Food and Drug Administration (FDA) approved bone anabolic agent, with reported stronger effects on bone mineral density (BMD), especially at the hip, than teriparatide. The recommended dose is 80 mcg subcutaneously once daily and its use is limited to a total duration of 2 years. Furthermore, because of the unknown relevance of the rodent osteosarcoma findings to humans, cumulative use of abaloparatide and parathyroid hormone analogues (eg, teriparatide) for more than 2 years during a patient’s lifetime is not recommended. On 9 April 2019, FDA approved the third bone anabolic agent, romosozumab (Evenity), a humanised antisclerostin monoclonal antibody and antagonist of Wnt signalling. Sclerostin is the product of the SOST gene and inhibits bone formation. It is administered subcutaneously monthly. Two separate subcutaneous injections, one immediately following the other, are needed to administer the recommended total dose of 210 mg. Its use is limited to a total duration of 1 year.\n\nThe approval of romosozumab heralded a chorus of statements such as ‘this is an extraordinary important drug’ and ‘it is a tremendous advance’ …